Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

Summary

This large-scale GWAS identified 389 genetic variants associated with age at menarche in women, implicating approximately 250 genes with notable enrichment in neural tissues. The findings demonstrate that pubertal timing is a highly polygenic trait with documented epidemiological links to adult disease risk. Mendelian randomisation analyses propose potential causal relationships between earlier menarche and certain health outcomes, suggesting that genetic factors affecting pubertal timing may partially explain known epidemiological associations.

Regional applicability

As a genomic study with predominantly European-ancestry populations (inferred from cohort names including LifeLines, kConFab/AOCS, and UK Biobank-linked collaborations), the findings are broadly applicable to United Kingdom research and clinical genetics practice, though generalisability to non-European ancestry groups remains limited.

Key measures

Age at menarche; genome-wide association P-values; population variance explained; effect sizes of genetic variants; tissue enrichment patterns; causal association estimates via Mendelian randomisation

Outcomes reported

The study identified 389 independent genetic signals associated with age at menarche across approximately 370,000 women, explaining roughly 7.4% of population variance and implicating around 250 genes. Mendelian randomisation analyses were used to explore potential causal associations between pubertal timing and adult disease risk.

Topic tags